Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated Immunoreceptor Tyrosine-based Activation Motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues...

Epithelial-mesenchymal transition (EMT) is a critical step and key factor during renal fibrosis. Preventing renal tubular EMT is important for delaying the progression of chronic kidney disease (CKD). P311, a highly conserved 8-kDa intracellular protein, has been indicated as an important factor in myofibroblast transformation and in the progression of fibrosis. However, the related studies on P311 on renal fibrosis are limited and the mechanisms of P311 in the progression of renal tubulointerstitial fibrosis remain largely unknown...

Cardiac Shock Wave Therapy (CSWT) improves myocardial perfusion and ameliorates cardiac remodeling after acute myocardial infarction (AMI), but the precise mechanisms remain obscure. Herein, we have applied CSWT to a rat model of AMI to demonstrate the arteriogenesis of coronary micrangium and protein expression changes in ischemic myocardium after CSWT. Four weeks after CSWT, the fraction shortening of rats was improved greatly and the cardiomyocyte apoptosis index was significantly lower than the AMI group (P < 0...

FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse. Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney. Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner. To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus...

TGFB1 (transforming growth factor beta 1) is a potent cytokine playing a driving role in development, fibrosis and cancer. It is synthesized as prodomain-growth factor complex that requires tethering to LTBP (latent transforming growth factor beta binding protein) for efficient secretion into the extracellular space. Upon release, this large latent complex is sequestered by anchorage to extracellular matrix (ECM) networks, from which the mature growth factor needs to be activated in order to reach its receptors and initiate signaling...

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is characterized by activated pancreatic stellate cells (PSCs), abundance of extracellular matrix (ECM), and production of cytokines and chemokines. Galectin 3 (GAL3), a β galactoside-specific lectin, contributes to PDAC development but its effects on the stroma and cytokine production are unclear. METHODS: The effect of recombinant human GAL3 (rGAL3) on activation of PSC, production of cytokines, and ECM proteins were determined by proliferation, invasion, cytokine array, and quantitative PCR...

The present study aimed to observe the effect of the biological functions of integrin-linked kinase (ILK) silencing combined with hyperthermia on Tca8113 cells. Lentivirus-mediated short hairpin RNA (shRNA)-targeting ILK was transfected into oral squamous cell carcinoma (OSCC) Tca8113 cells and, combined with hyperthermia, several experimental methods were used to detect their biological behavior in vitro. On the basis of in vitro experiments, Tca8113 cells were transplanted into nude mice models, and ILK-shRNA-lentivirus was injected into the nude mice transplanted tumor and combined with hyperthermia...

BACKGROUND: In this study we investigated the function of the non-catalytic region of tyrosine kinase adaptor protein 2 (NCK2) and its correlation with ITGB1 and ITGB4 integrins in driving ovarian cancer (OvCa) aggressiveness. We also evaluated whether NCK2 may influence prognosis in OvCa patients. METHODS: Nanofluidic technology was used to analyze expression of NCK2 in 332 OvCa patients. To evaluate mRNA expression of NCK2, integrins and VEGFA in OvCa cell lines, qRT-PCR was performed...

Erlotinib is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor, but the development of erlotinib resistance during chemotherapy can lead to treatment failure. To shed light on the erlotinib-resistant pathway, this study investigated the effect of combination therapy using curcumin- and erlotinib-loaded nanoparticles on the expression of αv β3 integrin and pyruvate dehydrogenase kinase 4 (PDK4) in an erlotinib-resistant SW480 colon cancer cell line. An erlotinib-resistant SW480 colon cancer cell line was produced by long-term exposure to erlotinib...

Hepatocellular carcinoma (HCC) is one of the major causes of cancer‑related mortality, and the prognosis of HCC patients is unsatisfactory. It is known that the occurrence and development of HCC involves numerous genes, as well as various steps and stages in the pathological process. High mobility group AT‑hook 1 (HMGA1) and integrin‑linked kinase (ILK) may be overexpressed in HCC and may serve important roles in the development of cancer; however, the relationship between HMGA1 and ILK in HCC has not been examined...

The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. Dysregulation of apoptosis has been linked with embryonal death and is involved in the pathophysiology of various diseases. Others and we previously demonstrated endothelial biology being intertwined with biochemical and structural composition of the subendothelial basement membrane. We now demonstrate that a three-dimensional growing environment significantly shields endothelial cells from cytokine-induced apoptosis...

Integrin-linked kinase (ILK) is a protein located in focal adhesion complexes that is linked to the cytoplasmic domain of integrin receptors. Together with PINCH and parvin, ILK forms the IPP complex, which is associated with conserved intracellular signalling pathways and integrin regulation of the actin cytoskeleton. ILK plays an essential role in a wide variety of cellular functions, including cell migration, differentiation, survival, and division. The present review summarizes recent evidence, suggesting a new role for ILK in organismal ageing and cellular senescence, indicating that ILK is a key regulator of longevity and premature cellular senescence induced by extracellular stressors...

Congenital heart defects, clinically identified in both small and large animals, are multifactorial and complex. Although heritable factors are known to have a role in cardiovascular disease, the full genetic aetiology remains unclear. Model organism research has proven valuable in providing a deeper understanding of the essential factors in heart development. For example, mouse knock-out studies reveal a role for the Integrin adhesion receptor in cardiac tissue. Recent research in Drosophila melanogaster (the fruit fly), a powerful experimental model, has demonstrated that the link between the extracellular matrix and the cell, mediated by Integrins, is required for multiple aspects of cardiogenesis...